Is COG4 p.Ser171= (c.513G>A) pathogenic?

COG4 p.Ser171= (c.513G>A) is classified Likely benign in COG4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). Rare (popmax 0.279%, mid); Associated with COG4-congenital disorder of glycosylation.

What condition is associated with COG4 p.Ser171= (c.513G>A)?

COG4 p.Ser171= (c.513G>A) is associated with COG4-congenital disorder of glycosylation (ClinVar).

How common is COG4 p.Ser171= (c.513G>A) in the general population?

COG4 p.Ser171= (c.513G>A) is rare (popmax 0.279%, mid) (gnomAD).

How is COG4-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COG4 p.Ser171=

c.513G>A · rs369063742 · VCV320379

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.279%, mid)

Conditions

COG4-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.11	GERP -0.7, phastCons 0.99
Overall
CADD	18.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.279% Middle Eastern · 17/6,084 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.0115% 186/1,614,024 alleles · rare exomes 160/1,461,880 · genomes 26/152,144 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.279%	358
Admixed American	0.035%	2,856
Remaining individualsnot grpmax-eligible	0.032%	3,124
European (non-Finnish)	0.01%	10,000
African / African-American	0.00801%	12,484
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0022%	45,539
Finnishnot grpmax-eligible	0.00156%	64,032

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COG4
Protein: p.Ser171=
Coding: c.513G>A
MANE Select: NM_015386
dbSNP: rs369063742
Type: single nucleotide variant
Location: chr16:70514366 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 1 PDB

Full COG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG4-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG4-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG4 p.Ser171Leu Uncertain significance ★ same residue
COG4 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
COG4 p.Arg733Trp Pathogenic/Likely pathogenic ★★ same condition
COG4 p.Glu614Ter Pathogenic ★★ same condition
COG4 p.Gly25Ter Pathogenic/Likely pathogenic ★★ same condition
COG4 p.Gly516Arg Pathogenic ★★ same condition
COG4 p.Ala251Thr Uncertain significance ★★ same condition
COG4 p.Ala544Val Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cog4-p-ser171 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown